rs539748

Variant names:

• chrX-114586876-C-T
• rs539748
• NM_000868.4:c.-147+2217C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000868.4(HTR2C):​c.-147+2217C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.81 (25533 hom., 25963 hem., cov: 22)
  • Failed GnomAD Quality Control
• Consequence: HTR2C NM_000868.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.66
• Publications: 1 publications found

Genes affected

HTR2C (HGNC:5295): (5-hydroxytryptamine receptor 2C) This gene encodes a seven-transmembrane G-protein-coupled receptor. The encoded protein responds to signaling through the neurotransmitter serotonin. The mRNA of this gene is subject to multiple RNA editing events, where adenosine residues encoded by the genome are converted to inosines. RNA editing is predicted to alter the structure of the second intracellular loop, thereby generating alternate protein forms with decreased ability to interact with G proteins. Abnormalities in RNA editing of this gene have been detected in victims of suicide that suffer from depression. In addition, naturally-occuring variation in the promoter and 5' non-coding and coding regions of this gene may show statistically-significant association with mental illness and behavioral disorders. Alternative splicing results in multiple different transcript variants. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HTR2C	NM_000868.4	c.-147+2217C>T		intron_variant	Intron 1 of 5	ENST00000276198.6	NP_000859.2
HTR2C	NM_001256760.3	c.-238+2217C>T		intron_variant	Intron 1 of 6		NP_001243689.2
HTR2C	NM_001256761.3	c.-147+2217C>T		intron_variant	Intron 1 of 5		NP_001243690.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HTR2C	ENST00000276198.6	c.-147+2217C>T		intron_variant	Intron 1 of 5	1	NM_000868.4	ENSP00000276198.1
HTR2C	ENST00000371951.5	c.-238+2217C>T		intron_variant	Intron 1 of 6	1		ENSP00000361019.1
HTR2C	ENST00000371950.3	c.-147+2217C>T		intron_variant	Intron 1 of 5	1		ENSP00000361018.3

Frequencies

GnomAD3 genomes AF: 0.811 AC: 88767 AN: 109485 Hom.: 25545 Cov.: 22

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.812

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.982

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.789

Gnomad NFE AF: 0.831

Gnomad OTH AF: 0.831

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.811 AC: 88768 AN: 109520 Hom.: 25533 Cov.: 22 AF XY: 0.817 AC XY: 25963 AN XY: 31788

African (AFR) AF: 0.737 AC: 22203 AN: 30144

American (AMR) AF: 0.811 AC: 8260 AN: 10180

Ashkenazi Jewish (ASJ) AF: 0.783 AC: 2059 AN: 2628

East Asian (EAS) AF: 0.982 AC: 3404 AN: 3466

South Asian (SAS) AF: 0.888 AC: 2236 AN: 2518

European-Finnish (FIN) AF: 0.881 AC: 4903 AN: 5566

Middle Eastern (MID) AF: 0.763 AC: 158 AN: 207

European-Non Finnish (NFE) AF: 0.831 AC: 43762 AN: 52654

Other (OTH) AF: 0.831 AC: 1232 AN: 1483

Alfa AF: 0.795 Hom.: 23548

Bravo AF: 0.800

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs539748; hg19: chrX-113821349;